title: [Genetic factors of angiogenic dysregulation in women with rheumatoid arthritis].
abstract: OBJECTIVE
  To study genotype distribution in the MMP and VEGF genes, angiogenesis regulators, and their combinations with genotypes in other cytokines genes with proangiogenic activity in female patients with rheumatoid arthritis (RA) and healthy individuals.
  
  
  METHODS
  509 Europeoid women from the eastern regions of Russia, including 374 healthy women aged 23-68 years and 135 female patients aged 27-66 years with RA, were examined. TNF-alpha gene promoter single nucleotide polymorphisms (SNP) -863 C --> A, TNFA -308 G --> A, TNFA -238 G --> A; IL 1beta-31 C --> T, IL4 -590 C --> T, IL6 -174 G --> C, IL10 -1082 G --> A and IL10 -592 A --> C; VEGF -2578 C --> A, VEGF +936 C --> T; MMP 2 -1306 C --> T, MMP 9 -1562 C --> T were investigated by the restriction analysis of amplification products.
  
  
  RESULTS
  The patients with RA show a preponderance of the combinations of genotypes in vascular endothelial growth factor (VEGF) synthesis inducers, which are related to the high-level production of this factor, and those of genotypes in the degradation of the extracellular matrix of MMP2 and MMP9, which characterize the low baseline elaboration of matrix metalloproteinases (MMP) with a high capability for their induced synthesis, which is specific to the dysregulated states of the angiogenesis control system. Along with MMP and VEGF genotypes, the combinations most commonly contain IL1beta, IL4, IL10, IL6, and TNF-alpha genotypes.
  
  
  CONCLUSIONS
  The study of the pathogenesis of RA must comprehensively investigate the role of the genes of the factors involved in the regulation of angiogenesis and inflammation, with particular emphasis on molecular genetic mechanisms for monitoring the baseline level of production of these regulatory factors.
authors.forename: V I
authors.initials: VI
authors.lastname: Konenkov
authors.forename: M A
authors.initials: MA
authors.lastname: Korolev
authors.forename: A V
authors.initials: AV
authors.lastname: Shevchenko
authors.forename: V F
authors.initials: VF
authors.lastname: Prokofyev
authors.forename: Yu B
authors.initials: YB
authors.lastname: Ubshaeva
authors.forename: O S
authors.initials: OS
authors.lastname: Sokolova
authors.forename: E A
authors.initials: EA
authors.lastname: Letyagina
authors.forename: G A
authors.initials: GA
authors.lastname: Dyubanova
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000503:physiopathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D012426:Russia; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D055815:Young Adult
chemical_list: D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9